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Naoko Shima, Ph.D.

Assistant Professor

Mailing Address:
University of Minnesota
Department of Genetics, Cell Biology, and Development
6-160 Jackson
321 Church St. SE
Minneapolis, MN 55455
USA
Education:
Ph. D., Saitama University, Japan, 1996
Office:
6-136 MCB
P:612-626-7830
F:612-626-6140

Email:
shima023@umn.edu

 Lab:
6-156 MCB
P:612-626-7831

Areas of Research Strength:

Mouse Cancer Genetics
Chromosome instability
Replication stress

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Research Techniques:

Mouse embryonic stem culture
Gene Knockout/Knockin
Cytogenetics
Cell cycle
Flow cytometric analysis of chromosome breaks

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Research Interests:

Dr. Shima's laboratory uses the Laboratory Mouse as a model system to investigate
the connection between chromosome instability and cancer. To discover new
genes or novel alleles that potentially affect chromosome stability and tumor
susceptibility in mice, they have previously conducted a whole-animal mutagenesis
screen. Using a highly sensitive flow cytometric assay that efficiently detects
chromosome breaks in blood cells, several mutations were recovered.  By positional
cloning and subsequent genetic experiments, they have identified mutations in two genes,
Polq and Mcm4.

Polq encodes DNA polymerase theta, a polymerase unique in that it also possesses
a helicase domain in a single polypeptide. POLQ is an error-prone polymerase that
can efficiently bypass an abasic site. This translesion activity plays a crucial role
in immunoglobulin gene somatic hypermutation, which underlies the generation
of high-affinity antibodies. Polq has two paralogs. The Lab is planning to investigate
these paralogs’ function in genome maintenance.

Mcm4 is an essential gene that is required for DNA replication. Dr. Shima's lab has recovered
a hypomorphic allele of Mcm4, which could cause replication defect or stress.  These
mutant mice are highly prone to mammary tumors. They are currently investigating
the connection among replication stress, chromosome instability, and cancer using
this novel mutant as a model.


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Selected Publications:

Shima N, Buske TR, and Schimenti JC (2007) Genetic screen for chromosome instability in mice: Mcm4 and breast cancer, Cell Cycle (in press)

Shima N, Alcaraz A, Liachko I, Buske TR, Anderws CA, Munroe RJ, Hartford SA, Tye BK, Schimenti JC (2007) A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice, Nature genetics 39: 93-98

Zan H, Shima N, Xu Z, Al-Qahtani A, Evinger III AJ, Zhong Y, Schimenti JC, Casali P (2005).  The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation, EMBO 24: 3757-3769

Shima N, Munroe RJ, Schimenti JC (2004) The mouse genomic instability mutation chaos1 is an allele of Polq that exhibits genetic interaction with Atm, Mol Cell Biol 23: 10381-10389

Reinholdt R, Ashley T, Schimenti J, Shima N (2003) Forward genetic screens for meiotic and mitotic recombination-defective mutants, In Genetic Recombination, Reviews and Protocols edited by Waldman AS, Methods in Molecular Biology, Humana Press, Totowa, NJ

Shima N, Hartford SA, Duffy T, Wilson LA, Schimenti KJ, Schimenti JC (2003) Phenotype-based identification of mouse chromosome instability mutants, Genetics 163: 1031-1040



To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
search menu should say PubMed
type Shima N in the avaliable line

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 Last modified on Friday, April 06, 2007